Genetic Risk Score Predicts Site-Specific Fractures

By Will Boggs MD

March 20, 2020

NEW YORK (Reuters Health) - A genetic risk score based on estimated bone-mineral density (eBMD) independently predicts site-specific fractures, researchers report.

Osteoporosis diagnosis and fracture-risk prediction are based on the combination of imaging (usually DXA) and clinical risk factors. Current fracture-risk prediction tools do not include information on trabecular or cortical bone microstructure and do not distinguish between differences in prediction of bone site-specific fractures.

Dr. Claes Ohlsson of Sahlgrenska Academy at the University of Gothenburg, Sweden, and colleagues compared the performances of bone-related genetic risk scores for the prediction of forearm, hip and vertebral fractures, as well as parameters of trabecular and cortical bone microstructure.

The ultrasound-based genetic risk score eBMD-GRS showed modest correlation with the DXA-based genetic risk scores for the femoral neck (FN-BMD-GRS) and lumbar spine (LS-BMD-GRS). These scores had a significant inverse association with estimated BMD, femoral neck BMD and lumbar spine BMD, respectively.

eBMD-GRS independently predicted wrist and vertebral fractures, while both the eBMD-GRS and the FN-BMD-GRS contributed to hip fracture prediction, the researchers report in The Journal of Clinical Endocrinology and Metabolism.

eBMD-GRS was also the major predictor of trabecular bone-microstructure parameters, whereas both the FN-BMD-GRS and the eBMD-GRS contributed independent information for prediction of cortical bone area and cortical density.

"We propose that eBMD-GRS captures unique information of trabecular bone microstructure useful for the prediction of forearm and vertebral fractures," the authors conclude. "The findings in the present study may facilitate personalized medicine to predict different fracture types as well as cortical and trabecular bone microstructure parameters separately."

"Personalized medicine has the potential to customize therapy with the best response and highest safety margin to ensure better patient care, by enabling each patient to receive earlier diagnoses, risk assessments, and optimal treatments," they add.

Dr. Stuart K. Kim of Stanford University Medical Center, in California, who has also developed a polygenic risk score for BMD, osteoporosis and fracture, told Reuters Health by email, "Physicians should learn that genetic testing for low BMD may be part of standard of care in the future. eBMD-GRS is directly relevant to diagnosing osteoporosis and is also effective at predicting fracture via its effect on BMD."

He noted that eBMD-GRS is essentially identical to the genetic risk score his group developed earlier, which the authors did not mention and which he considers already out of date.

"The algorithm for eBMD developed 2 years ago (LASSO4) outperforms eBMD-GRS," he said. "This tempers my enthusiasm for this manuscript."

Dr. Tuan V. Nguyen of Garvan Institute of Medical Research, Sydney, Australia, who recently reviewed the state of the art of individualized fracture-risk assessment, said, "Genetics does contribute to an individual's propensity to fracture."

Apart from BMD, clinicians should take "family history of fracture into account in the assessment of a patient's fracture risk," he told Reuters Health by email.

"However, because the contribution of eBMD-GRS to fracture risk is modest, it alone cannot be a reliable indicator of fracture risk," he said. "It must be used with clinical risk factors, such as a history of fracture, fall, and comorbidities."

"This 'genetic signature' was developed based on genetic data collected from Caucasian populations, and it may not be applicable to non-Caucasian populations," added Dr. Nguyen, who was not involved in the research. "We need more genomic studies in non-Caucasian ethnicities."

Dr. Ohlsson did not respond to a request for comments.

SOURCE: The Journal of Clinical Endocrinology and Metabolism, online February 18, 2020.